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Zhi-Dan Fan, Ya-Yuan Zhang, Yi-Hong Guo, Na Huang, Hui-Hui Ma, Hui Huang, Hai-Guo Yu
Interleukin (IL)-17 producing T helper (Th17) cells are major effector cells in the pathogenesis of rheumatoid arthritis (RA). The P2X7 receptor (P2X7R) has emerged as a potential site in the regulation of inflammation in RA but little is known of its functional role on the differentiation of Th17 cells. This study investigates the in vitro and in vivo effects of P2X7R on Th17 cell differentiation during type II collagen (CII) induced experimental arthritis model. In CII-treated dendritic cells (DCs) and DC/CD4(+) T coculture system, pretreatment with pharmacological antagonists of P2X7R (Suramin and A-438079) caused strong inhibition of production of Th17-promoting cytokines (IL-1β, TGF-β1, IL-23p19 and IL-6)...
October 24, 2016: Scientific Reports
Ma Ke, Xi Chen, Jia-Cheng Chen, Ying Wang, Xi-Meng Zhang, Fan Huang, Jun-Jiong Zheng, Xiong Chen, Wei Yu, Ke-Ling Cheng, Yan-Qing Feng, Huai-Yu Gu
Rifampicin, a broad-spectrum antibiotic, has neuroprotective, immunosuppressive, and anti-inflammatory properties. However, the effect of rifampicin on autoimmune disorders of the nervous system is not clear. In this study, we investigated whether rifampicin was beneficial for myelin oligodendrocyte glycoprotein peptide (MOG33-35 )-induced female C57BL/6 experimental autoimmune encephalomyelitis (EAE) mice, the well-established animal model of multiple sclerosis (MS). Rifampicin treatment (daily from the first day after EAE immunization) remarkably attenuated clinical signs and loss of body weight, which are associated with suppression of inflammatory infiltration and demyelination in spinal cords of EAE mice...
October 23, 2016: Journal of Neurochemistry
Soo Young Kim, Min Seok Hur, Byung Gon Choi, Min Jung Kim, Yang Won Lee, Yong Beom Choe, Kyu Joong Ahn
Psoriasis is a polygenic and multifactorial disease showing ethnic differences in terms of its severity and frequency. Therapies targeting interleukin 17A (IL-17A), interleukin 17 receptor (IL-17R), and Janus kinases (JAKs) are in clinical development for the treatment of psoriasis, and their success suggests the essential role of these molecules in psoriasis. To investigate the genetic susceptibility in T helper 17 (Th17) cell signal transduction pathways for promoting psoriasis, we performed candidate gene and linkage disequilibrium analysis...
October 24, 2016: Clinical and Experimental Immunology
Naif O Al-Harbi, Ahmed Nadeem, Mohammed M Al-Harbi, Khairy M A Zoheir, Mushtaq A Ansari, Ahmed M El-Sherbeeny, Khalid M Alanazi, Moureq R Alotaibi, Sheikh F Ahmad
Psoriatic inflammation has been shown to be associated with cardiovascular dysfunction and systemic inflammation. Recently, psoriasis has also been linked to hepatic disorders, however underlying mechanism connecting the two are unknown. IL-17A being a central pro-inflammatory cytokine in the pathogenesis of psoriasis may be involved in hepatic inflammation through its receptor and downward signaling; however so far no study has investigated IL-17A related signaling in the liver during psoriasis in a murine model...
October 18, 2016: Immunobiology
Miao Yu, Qi Long, Huan-Huan Li, Wei Liang, Yu-Hua Liao, Jing Yuan, Xiang Cheng
Myocardial injuries in viral myocarditis (VMC) are caused by viral infection and related autoimmune disorders. Recent studies suggest that IL-9 mediated both antimicrobial immune and autoimmune responses in addition to allergic diseases. However, the role of IL-9 in viral infection and VMC remains controversial and uncertain. In this study, we infected Balb/c mice with Coxsackievirus B3 (CVB3), and found that IL-9 was enriched in the blood and hearts of VMC mice on days 5 and 7 after virus infection. Most of IL-9 was secreted by CD8(+) T cells on day 5 and CD4(+) T cells on day 7 in the myocardium...
2016: Frontiers in Immunology
Marco Tucci, Stefania Stucci, Anna Passarelli, Stella D'Oronzo, Franco Silvestris
Interleukin-17A (IL-17A) promotes the osteoclast (OC)-like differentiation of dendritic cells (DCs) in multiple myeloma (MM), and contributes to the pathogenesis of myeloma bone disease (MBD). In our study, EVR significantly abrogated the in vitro OC-like activity of DCs from 12 MM patients. Exploring the EVR effects, we found that the inhibition of the osteo-erosive activity of OC-DCs was mostly due to the blockade of signals driven by the IL-17A receptor toward CEBPbeta/MAFB axis Therefore, MM patients with MBD would probably benefit from mTOR inhibition...
October 17, 2016: Experimental Hematology
Zhengyu Shen, Chenping Zhang, Zengtong Zhou, Wei Liu, Linjun Shi, Xuemin Shen
OBJECTIVE: To investigate the potential role of interleukin (IL)-17A and its targeting microRNAs (miRNAs) in oral lichen planus (OLP). STUDY DESIGN: We compared the IL-17A expression levels in biopsies from patients with OLP (n = 50) against normal controls (n = 19) by using reverse transcription quantitative polymerase chain reaction (RT-qPCR) and Western blot analyses, identified the targeting miRNAs of IL-17A, and examined the miRNA expression levels in OLP...
November 2016: Oral Surgery, Oral Medicine, Oral Pathology and Oral Radiology
Marisa de Carvalho Borges, Tharsus Dias Takeuti, Guilherme Azevedo Terra, Betânia Maria Ribeiro, Virmondes Rodrigues-Júnior, Eduardo Crema
Background: Surgical trauma triggers an important postoperative stress response characterized by significantly elevated levels of cytokines, an event that can favor the emergence of immune disorders which lead to disturbances in the patient's body defense. The magnitude of postoperative stress is related to the degree of surgical trauma. Aim: To evaluate the expression of pro-inflammatory (TNF-α, IFN-γ, IL-1β, and IL-17) and anti-inflammatory (IL-4) cytokines in patients submitted to conventional and single-port laparoscopic cholecystectomy before and 24 h after surgery...
July 2016: Arquivos Brasileiros de Cirurgia Digestiva: ABCD, Brazilian Archives of Digestive Surgery
Matthew Gordon Varga, Maria Blanca Piazuelo, Judith Romero-Gallo, Alberto G Delgado, Giovanni Suarez, Morgan E Whitaker, Uma S Krishna, Rachna V Patel, Eric P Skaar, Keith T Wilson, Holly M Scott Algood, Richard M Peek
Helicobacter pylori induces chronic gastritis in humans and infection can persist for decades. One H. pylori strain-specific constituent that augments disease risk is the cag pathogenicity island. The cag island encodes a type IV secretion system (T4SS) that translocates DNA into host cells. Toll-like receptor 9 (TLR9) is an innate immune receptor that detects hypo-methylated CpG DNA motifs. In this study, we sought to define the role of the H. pylori cag T4SS on TLR9-mediated responses in vivo H. pylori strain PMSS1 or its cagE(-) mutant, which fails to assemble a T4SS, were used to infect wild-type or Tlr9(-/-) C57BL/6 mice...
October 6, 2016: American Journal of Physiology. Gastrointestinal and Liver Physiology
Naoyuki Makita, Jun Ishiguro, Keisuke Suzuki, Futoshi Nara
OBJECTIVES: Recently, there has been a growing interest in the mechanism of action of dichloroacetate (DCA) for T-cell differentiation; however, this mechanism has not been elucidated in detail. Therefore, this study aimed to investigate the mechanism of action of DCA for Treg and Th17 differentiation with pyruvate dehydrogenase kinase (PDHK) inhibitor (AZD7545) and PDHK knockdown. METHODS: Inhibitory activity of DCA and AZD7545 against recombinant PDHK and intracellular PDH phosphorylation was measured...
October 19, 2016: Journal of Pharmacy and Pharmacology
David Harrison
Hypertension remains an enormous health care burden that affects one third of the population. Despite its prevalence the cause of most cases of hypertension remains unknown. Our laboratory has defined a novel mechanism for hypertension involving adaptive immunity. We found that mice lacking lymphocytes (RAG-1 mice) develop blunted hypertensive responses to a variety of stimuli including chronic angiotensin II infusion, DOCA-salt challenge and norepinephrine infusion. Adoptive transfer of T cells, but not B cells, restores the hypertensive responses to these stimuli...
September 2016: Journal of Hypertension
Charles Nicaise, Laura Weischelbaum, Liliane Schandene, Valérie Gangji, Florence Dehavay, Joanna Bouchat, Benoît Balau, Thomas Vogl, Muhammad S Soyfoo
OBJECTIVES: To determine the role of S100A8/A9 in the pathogenesis of primary Sjögren's syndrome (pSS). METHODS: The serum levels of S100A8/A9 were determined in pSS patients and healthy controls by ELISA. The expression of S100A8/A9 in salivary glands was assessed by immunohistochemistry. The phenotype of S100A8+ and S100A9+ cells was identified using double immunofluorescence. The effects of S100A8/A9 on cytokine production by peripheral blood mononuclear cells (PBMCs) from pSS patients were determined in vitro by flow cytometry...
October 7, 2016: Clinical and Experimental Rheumatology
Philip Mease, Iain B McInnes
INTRODUCTION: Psoriatic arthritis (PsA) is an immune-mediated chronic inflammatory arthropathy associated with impaired physical function and reduced quality of life. Biologic therapies that target tumor necrosis factor (anti-TNF) have significantly improved clinical outcomes. Partial, non- and transient responses remain common comprising significant unmet clinical need. New therapies with novel modes of action are urgently required. OBJECTIVES: The interleukin (IL)-17 pathway has recently been attributed a critical role in the pathogenesis of spondyloarthritides...
June 2016: Rheumatol Ther
Zheng Jun Li, Dae-Kyoung Choi, Kyung-Cheol Sohn, Seul Ki Lim, Myung Im, Young Lee, Young-Joon Seo, Chang Deok Kim, Jeung-Hoon Lee
BACKGROUND: Interleukin-17A (IL-17A) is mainly secreted from Th17 cells that are activated by various stimuli including CpG oligodeoxynucleotide, a Toll-like receptor 9 (TLR9) ligand. Recently, it has been demonstrated that keratinocytes play an important role in the pathogenesis of psoriasis. OBJECTIVE: To investigate the potential role of keratinocytes, we examined whether TLR9 ligand CpG induces IL-17A expression in keratinocytes. METHODS: We used HaCaT keratinocytes as a model system, and determined CpG-induced IL-17A using enzyme-linked immunosorbent assay and Western blot...
October 2016: Annals of Dermatology
Cecilia K Andersson, Alexandra Adams, Prasad Nagakumar, Cara Bossley, Atul Gupta, Daphne De Vries, Afiqah Adnan, Andrew Bush, Sejal Saglani, Clare M Lloyd
BACKGROUND: Neutrophils and IL-17A have been linked mechanistically in models of allergic airways disease and have been associated with asthma severity. However, their role in paediatric asthma is unknown. OBJECTIVES: To investigate the role of neutrophils and the IL-17A pathway in mediating paediatric severe therapy resistant asthma (STRA). METHODS: Children with STRA (n=51, age 12.6 (6 -16.3) years) and non-asthmatic controls (n=15, age 4...
October 13, 2016: Journal of Allergy and Clinical Immunology
Robert Bissonnette, Judilyn Fuentes-Duculan, Shunya Mashiko, Xuan Li, Kathleen M Bonifacio, Inna Cueto, Mayte Suárez-Fariñas, Catherine Maari, Chantal Bolduc, Simon Nigen, Marika Sarfati, James G Krueger
BACKGROUND: Palmoplantar pustular psoriasis (PPPP) is a variant of psoriasis, which has significant negative impact on quality of life. The cellular and molecular inflammatory pathways involved in PPPP have not been well studied. OBJECTIVE: Study the expression of cytokines and chemokines involved in the IL-17/IL-23 axis in palmoplantar pustular psoriasis and other difficult to treat psoriasis areas (palms, scalp, elbows and lower legs). METHODS: Skin biopsies were performed on a total of 80 patients with PPPP, non-pustular palmoplantar psoriasis (NPPPP), or psoriasis located on elbows, knees and scalp as well as 10 healthy subjects...
September 29, 2016: Journal of Dermatological Science
Stefania Nicola, Angela Amoruso, Francesca Deidda, Marco Pane, Serena Allesina, Luca Mogna, Mario Del Piano, Giovanni Mogna
GOALS: To investigate the modulation of human cytokines by Bifidobacterium longum strains isolated from Centenarians. In particular, we measured the production of interleukin (IL)-12p70, interferon-γ, IL-17A, and IL-4 from human peripheral blood mononuclear cells after stimulation with live bacteria. BACKGROUND: Probiotics may inhibit pathogens and modulate the immune system, bringing a beneficial effect on human health. Among the probiotic strains, bifidobacteria play a key role in the maturation of the host's immune system...
November 2016: Journal of Clinical Gastroenterology
Keshav Raj Sigdel, Lihua Duan, Yin Wang, Weiping Hu, Ning Wang, Qingyi Sun, Qingyan Liu, Xiaocong Liu, Xianghua Hou, Ao Cheng, Guixiu Shi, Yanlin Zhang
Systemic lupus erythematosus (SLE) is a chronic autoimmune disease characterized by aberrant T cell immune response. Diffuse proliferative lupus nephritis (LN-IV) is the most common, severe, and active form of lupus nephritis. In this study, we investigated the production of Th1, Th2, and Th17 cytokines in prediction of active form of LN-IV. ProcartaPlex multiplex immunoassays panels were used for detection of serum Th1, Th2, and Th17 cytokines profiling. Th1 and Th17 cytokines (IL-18, IFN-γ, IL-12p70, IL-6, and IL-17A) were considerably expressed in the serum of lupus nephritis IV patients in comparison to the healthy control...
2016: Mediators of Inflammation
Y Yamada, E Vandermeulen, T Heigl, J Somers, A Vaneylen, S E Verleden, H Bellon, S De Vleeschauwer, E K Verbeken, D E Van Raemdonck, R Vos, G M Verleden, W Jungraithmayr, B M Vanaudenaerde
The single most important cause of late mortality after lung transplantation is chronic lung allograft dysfunction (CLAD). However, the pathological development of CLAD was not as simple as previously presumed and subclassification phenotypes, bronchiolitis obliterans syndrome (BOS) and restrictive CLAD (rCLAD), have been introduced. We want to re-investigate how CLAD manifests in the murine orthotopic lung transplant model and investigate the role of interleukin 17A (IL-17A) within this model. Orthotopic LTx was performed in CB57Bl6, IL-17 WT and IL-17 KO mice...
October 10, 2016: Transplant Immunology
Kenneth I Strauss, Kost V Elisevich
BACKGROUND: Epilepsy patients have distinct immune/inflammatory cell profiles and inflammatory mediator levels in the blood. Although the neural origin of inflammatory cells and mediators has been implied, few studies have measured these inflammatory components in the human brain itself. This study examines the brain levels of chemokines (8), cytokines (14), and vascular injury mediators (3) suspected of being altered in epilepsy. METHODS: Soluble protein extracts of fresh frozen resected hippocampus, entorhinal cortex, and temporal cortex from 58 medically refractory mesial temporal lobe epilepsy subjects and 4 nonepileptic neurosurgical subjects were assayed for 25 inflammation-related mediators using ultrasensitive low-density arrays...
October 13, 2016: Journal of Neuroinflammation
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